Amidinoureas and amidinothioureas

ABSTRACT

Antibacterial and antifungal mono- and disubstituted amidinoureas and amidinothioureas are obtained by interaction of quanidines and isocyanates or isothiocyanates.

This application is a division of copending application Ser. No.391,473, filed Aug. 24, 1973, which is a division of application Ser.No. 79,266, filed Oct. 8, 1970 and now U.S. Pat. No. 3,798,269, which isa division of copending application Ser. No. 749,986, filed Aug. 5, 1968and now U.S. Pat. No. 3,652,766, which is a continuation-in-part ofapplication Ser. No. 556,897, filed June 13, 1966 and now abandoned,which is a continuation-in-part of application Ser. No. 462,077, filedJune 7, 1965 and now abandoned. Application Ser. No. 91,164 is also adivision of application Ser. No. 749,986 and is now U.S. Pat. No.3,692,625.

This invention relates to chemical compounds classified as amidinoureasand amidinothioureas, to the preparation of the same and to a processfor combatting microorganisms therewith.

The invention sought to be patented, in its process aspect, is describedas residing in the concept of applying to a medium, in order to obviateobjectionable or deleterious microorganisms, a composition of mattercontaining a chemical compound selected either from the group ofcompounds which, in the form of the free base, has the structuralformula ##STR1## wherein X is a member of the group consisting of oxygenand sulfur and one of R and R' is alkyl and the other of R and R' is amember of the group consisting of hydrogen and alkyl, the total numberof carbon atoms in R and R' being 8-24; or from the group of compoundswhich, in the form of the free-base, has the structural formula ##STR2##wherein: X is a member of the group consisting of oxygen and sulfur; oneof Y and Y' is a member of the group consisting of hydrogen, alkylcontaining 1-18 carbon atoms, alkenyl containing 3-18 carbon atoms,alkoxyalkyl containing 3-17 carbon atoms, alkylthioalkyl containing 3-17carbon atoms, cycloalkyl containing 3-8 carbon atoms di(loweralkyl)aminoalkyl containing 4-10 carbon atoms, morpholinoalkylcontaining 6-10 carbon atoms, and piperidinaolkyl containing 7-11 carbonatoms; and the other of Y and Y' is a member of the group consisting ofalkenyl containing 3-18 carbon atoms, alkoxyalkyl containing 3-17 carbonatoms, alkylthioalkyl containing 3-17 carbon atoms, cycloalkylcontaining 3-8 carbon atoms, di(lower alkyl)aminoalkyl containing 4-10carbon atoms, morpholinoalkyl containing 6-10 carbon atoms, andpiperidinoalkyl containing 7-11 carbon atoms.

The invention sought to be patented, in its composition aspect, isdescribed as residing in the concept of a chemical compound having thestructural formula ##STR3## wherein: X is oxygen or sulfur; Y" and Y'"may be the same or different and are members of the group consisting ofalkyl containing 1-8 carbon atoms, alkenyl containing 3-18 carbon atoms,alkoxyalkyl containing 3-17 carbon atoms, alkylthioalkyl containing 3-17carbon atoms, cycloalkyl containing 3-8 carbon atoms, di(loweralkyl)aminoalkyl containing 4-10 carbon atoms, morpholinoalkylcontaining 6-10 carbon atoms or piperidinoalkyl containing 7-11 carbonatoms; Y" also is hydrogen when X is oxygen and Y'" is alkenylcontaining 3-18 carbon atoms, alkylthioalkyl containing 3-17 carbonatoms, di(lower alkyl)aminoalkyl containing 4-10 carbon atoms,morpholinoalkyl containing 6-10 carbon atoms or piperidinoalkylcontaining 7-11 carbon atoms; and Y" also is hydrogen when X is sulfurand Y'" is alkyl containing 8-18 carbon atoms, alkoxyalkyl containing3-17 carbon atoms, alkylthioalkyl containing 3-17 carbon atoms,cycloalkyl containing 3-8 carbon atoms, di(lower alkyl)aminoalkylcontaining 4-10 carbon atoms, morpholinoalkyl containing 6-10 carbonatoms or piperidinoalkyl containing 7-11 carbon atoms.

The compounds of Formulas I, II and III are basic substances whichinteract with one or, in the instances of the morpholinoalkyl andpiperidinoalkyl compounds, two or three equivalents of an organic orinorganic acid to form the corresponding acid-addition salts. Theseacid-addition salts and the free bases of course have the commonstructural entity represented by the structural formulas, Formula I,Formula II, or Formula III, as the case may be. The acid-addition saltsare the full equivalents of the free base forms, and the new compoundsof this invention include both the free bases and the acid-additionsalts thereof. The novel feature of the compounds of the invention thusresides in the concept of the bases and the acid-addition salts thereof.The novel feature of the compounds of the invention thus resides in theconcept of the bases and cationic forms of the new amidinoureas andamidinothioureas and not in any particular acid moiety or acid anionassociated with the salt forms of our compounds; rather, the acidmoieties or anions which can be associated in the salt forms are inthemselves neither novel nor critical and therefore can be any acidanion or acid-like substance capable of salt formation with bases. Itwill be appreciated that in aqueous solutions the base form and theacid-addition salt form of the compounds of the invention possess acommon protonated cation of ammonium ion.

Thus, the acid-addition salts discussed above and claimed herein areprepared from any organic acid, inorganic acid (including organic acidshaving an inorganic group therein), or organo-metallic acid asexemplified by organic mono- and poly-carboxylic acids such as found,for example, in Beilstein's Organische Chemie, 4th ED., Volumes III, IV,IX, X, XIV, XVII, XIX, XXI, XXII, and XXV; organic mono- andpolysulfonic and -sulfonic acids such as found, for example in BeilsteinVolumes VI, XI, XVI, and XXII; organic phosphonic and phosphinic acidssuch as found, for example, in Beilstein Volumes XI and XVI; organicacids of arsenic and antimony sych as found, for example, in BeilsteinVolume XVI; organic heterocyclic carboxylic, sulfonic, and sulfinicacids such as found, for example in Beilstein Volumes XVIII, XXII, andXXV; acidic ion-exchange resins; and inorganic acids of any acid formingelement or combination of elements such as found in Mellor,Comprehensive Treatise on Inorganic and Theoretical Chemistry,Longman's, Green and Co., New York, N.Y., Volumes I-XVI. In addition,other salt-forming compounds which are acidic in their chemicalproperties but which are not generally considered as acids in the samesense as carboxylic or sulfonic acids are also considered to be amongthe numerous acids which can be used to prepare acid-addition salts ofthe compounds of the invention. Thus there are also comprehended acidicphenolic compounds such as found, for example, in Volume VI orBeilstein, acidic compounds having activated or acidic hydrogen atoms,as for example, picrolonic acid, or barbituric acid derivatives havingan acidic proton such as found, for example, in Cox et al. MedicinalChemistry, Vol. IV, John Wiley and Sons, Inc., New York, N.Y. (1959).Also comprehended as salt forming agents are so-called Lewis acids whichlack a pair of electrons in the outer "electron shell" and react withbasic compounds having an unshared pair of electrons to form salts, forexample boron trifluoride.

Representative acids for the formation of the acid-addition saltsinclude formic acid, acetic acid, isobutyric acid,alpha-mercaptopropionic acid, trifluoroacetic acid, malic acid, fumaricacid, succinic acid, succinamic acid, glutamic acid, tartaric acid,oxalic acid, pyromucic acid, citric acid, lactic acid, glycolic acid,gluoconic acid, saccharic acid, ascorbic acid, penicillin, benzoic acid,phthalic acid, salicyclic acid, 3,5-dinitrobenzoic acid, anthranilicacid, pamoic acid, cholic acid, 2-pyridinecarboxylic acid,3-hydroxy-2-naphthoic acid, picric acid, quinic acid, tropic acid,3-indoleacetic acid, barbituric acid, sulfamic acid, methanesulfonicacid, ethanesulfonic acid, isethionic acid, benzenesulfonic acid,p-toluenesulfonic acid, butylarsonic acid, methanephosphonic acid,acidic resins, hydrofluoric acid, hydrochloric acid, hydrobromic acid,hydriodic acid, perchloric acid, nitric acid, sulfuric acid, phosphoricacid, hydrocyanic acid, phosphotungstic acid, molybdic acid, arsenicacid, and the like.

The acid-addition salts are prepared in conventional fashion, forinstance either by direct mixing of the acid and the base or, when thisis not appropriate, by dissolving either or both of the acid and thebase separately in a suitable solvent and mixing the two solutions, orby dissolving both the acid and the base together in a solvent. Theresulting acid-addition salt is isolated by filtration, if it isinsoluble in the reaction medium, or by evaporation of the reactionmedium to leave the acid-addition salt as a residue.

Our new bases of Formulas I, II and III and the acid-addition saltsthereof have biocidal and biostatic properties and are particularlyuseful as antibacterial and antifungal agents. Thus, when tested bystandard serial dilution procedures, these compounds were found to havebactericidal, bacteriostatic, fungicidal, and fungistatic activity invitro. Moreover, some of these compounds are effective in the control ofphytophathogenic microorganisms, for instance, having useful activityagainst bacterial and fungal infections in plants, for example lateblight (Phytophthora infestans ) and bacterial spot (Xantomonasvesicatoria) on tomatoes (Lycopersicon esculentum) and bean rust(Uromyces phaseoli typica) on pinto beans (Phaseolus vulgaris).

The new bases of Formulas I, II and III and the acid-addition saltsthereof are useful as disinfecting and sanitizing agents for applicationto living and non-living surfaces by conventional swabbing, padding,spraying, immersing, rinsing, and the like techniques. Depending on theparticular purpose involved, the compounds are used in aqueous solution,as in water or in aqueous detergent solutions, or in the form ofsolutions in organic solvents.

The acid-addition salts of the bases of Formulas I, II and III areuseful not only as disinfecting and sanitizing agents, asabove-indicated, but are also useful as characterizing or identifyingderivatives of the free bases and in isolation or purificationprocedures. Moreover, the acid-addition salts react with strong bases,such as alkali metal hydroxides, to generate the free bases, andaccordingly all of the salts, regardless of considerations ofsolubility, toxicity, physical form, or the like of a particular speciesof acid-addition salt, are useful for the purposes of our inventionsince they are sources of the free bases.

It will be appreciated from the above that if one or more of thecharacteristics, such as solubility, molecular weight, physicalappearance, toxicity, or the like of a given acid-addition salt renderit unsuitable for the particular desired purpose, as for example, use asan antibacterial agent or in an isolation or purification procedure, orthe like, the acid-addition salt can be converted to the free base andthen to another, more suitable acid-addition salt, for instance apharmaceutically-acceptable salt when a pharmaceutical use is involved.

The 1-(R)-amidino-3-(R')-ureas and the 1 -(R)-amidino-3-(R')-thioureasof Formula I and the 1-(Y)-amidino-3-(Y')-ureas and the1-(Y-amidino)-3-(Y')-thioureas of Formula II, except those specieswherein R' and Y' are hydrogen, are obtained by interacting a1-(R)-guanidine or a 1-(Y)-guanidine with approximately one molecularproportion of an isocyanate or isothiocyanate having the structuralformula

R' -- NCX Formula IV

for the preparation of the Formula I compounds and having the structuralformula

y' -- NCX Formula V

for the preparation of the Formula II compounds, wherein: R is hydrogenor alkyl and R' is alkyl, the total number of carbon atoms in R and R'being 8-24;

Y is a member of the group consisting of hydrogen, alkyl containing 1-8carbon atoms, alkenyl containing 3-18 carbon atoms, alkoxyalkylcontaining 3-17 carbon atoms, alkylthioalkyl containing 3-17 carbonatoms, cycloalkyl containing 3-8 carbon atoms, di(lower alkyl)aminoalkylcontaining 4-10 carbon atoms, morpholinoalkyl containing 6-10 carbonatoms, and piperidinoalkyl containing 7-11 carbon atoms; Y' is a memberof the group consisting of alkenyl containing 3-18 carbon atoms,alkoxyalkyl containing 3-17 carbon atoms, alkylthioalkyl containing 3-17carbon atoms, cycloalkyl containing 3-8 carbon atoms, di(loweralkyl)aminoalkyl containing 4-10 carbon atoms, morpholinoalkylcontaining 6-10 carbon atoms, and piperidinoalkyl containing 7-11 carbonatoms; and X in each instance is a member of the group consisting ofoxygen and sulfur. In a convenient method of carrying out this reaction,sodium and dry acetone are mixed together, and then the guanidine in theform of its hydrochloride or sulfate is added, and this is followed bythe isocyanate or isothiocyanate reactant; approximately equimolaramounts each of the sodium, the 1-(R or Y)-guanidine salt, and theisocyanate or isothiocyanate are used, and the method can be carried outat room temperature.

The 1-(R)-amidino-3-(R')-ureas of Formula I wherein R' is hydrogen andthe 1-(Y)-3-(Y')-ureas of Formula II wherein Y' is hydrogen are obtainedby hydrolyzing with a strong acid a 1-(R)-3-cyanoguanidine having thestructural formula ##STR4## or a 1-(Y)-3-cyanoguanidine having thestructural formula ##STR5## wherein R is alkyl containing 8-24 carbonatoms and Y is a member of the group consisting of alkenyl containing3-18 carbon atoms, alkoxyalkyl containing 3-17 carbon atoms,alkylthioalkyl containing 3-17 carbon atoms, cycloalkyl containing 3-8carbon atoms, di(lower alkyl)aminoalkyl containing 4-10 carbon atoms,morpholinoalkyl containing 6-10 carbon atoms, and piperidinoalkylcontaining 7-11 carbon atoms. Conveniently, this hydrolysis is carriedout by refluxing the 1-(R or Y)-3-cyanoguanidine with concentratedhydrochloric acid.

The 1-(R)-amidino-3-(R')-thioureas of Formula I wherein R' is hydrogenand the 1-(Y)-amidino-3(-Y')-thioureas of Formula II wherein Y' ishydrogen are obtained by interacting one equivalent of a1-(R)-3-cyanoguanidine having the structural formula V or a1-(Y)-3-cyanoguanidine having the structural Formula VI, as hereinabovedefined, with two equivalents of hydrogen sulfide. Conveniently thecyanoguanidine is heated with a saturated lower alkanolic solution ofhydrogen sulfide at 70°-80° C. in a closed vessel. For best results, thereaction mixture is heated for 48 hours or longer.

The 1-(Y")-amidino-3-(Y'")-ureas and the1-(Y"-amidino)-3-(Y'")-thioureas of Formula III are obtained byinteracting a 1-(Y")-guanidine with approximately one molecularproportion of an isocyanate or isothiocyanate having the structuralformula

Y'" -- NCX Formula VIII

wherein Y", Y'", and X have the same respective meanings indicatedhereinabove in relation to Formula III. In a convenient method ofcarrying out this reaction, sodium and dry acetone are mixed together,and then the guanidine in the form of its hydrochloride or sulfate isadded, and this is followed by the isocyanate or isothiocyanatereactant; approximately equimolar amounts each of the sodium, the1-(Y")-guanidine salt, and the isocyanate or isothiocyanate are used,and the method can be carried out at room temperature.

The intermediates required for the preparation of our new compounds areall old and well-known classes of compounds and are readily obtained byconventional preparative procedures. Thus, for example, the isocyanatesand isothiocyanates of Formulas IV, V and VIII are obtained byinteraction of phosgene or thiophosgene with a primary amine having theformula R'--NH₂, Y'--NH₂ or Y'"--NH₂, or the hydrochlorides thereof,wherein R', Y', and Y'" have the same significance as indicatedhereinabove in connection with Formulas IV, V and VIII. The1-(R)-3-cyanoguanidines of Formula VI and the 1-(Y)-3-cyanoguanidines ofFormula VII are obtained, for example, by interaction of dicyanamide, ormetal salt thereof, with a primary amine having the formula R--NH₂ orY--NH₂ or acid-addition salt thereof, wherein R and Y have the samesignificance indicated hereinabove in connection with Formulas VI andVII, respectively. The 1-(R, Y and Y")-guanidines include guanidineitself, which is readily available, and the substituted guanidines whichare obtained, for example, by interaction of ammonium chloride with asubstituted cyanamide having the formula R--NH--CN, Y--NH--CN orY"--NH--CN, or by interaction of 2-methyl-2-thiopseudourea sulfate witha primary amine having the formula R--NH₂, Y--NH₂ or Y"--NH₂, wherein R,Y and Y" have the same significance indicated hereinabve in connectionwith Formula VI, VII and VIII, respectively.

We especially prefer those compounds of this invention in which R and R'in Formula I contain a total of 9-16 carbon atoms, Y and Y' in FormulaII, and Y" and Y'" in Formula III contain a total of 9-16 carbon atomssince these preferred compounds have particularly high antibacterial andantifungal activities and hence have been found to be particularlyuseful as antibacterial and antifungal agents.

The chemical structures of the compounds of this invention followed fromthe modes of preparation from the elementary analyses of the products,and from spectral data on the compounds.

Our invention is illustrated by the following examples without, however,being limited thereto.

EXAMPLE 1

A. 4.1 g. of sodium was added to 200 ml. of dry acetone and the mixturewas refluxed for ten minutes and after the resulting mixture cooled toroom temperature there was added in one portion, with strong stirring,19.1 g. of guanidine hydrochloride. The resulting reaction mixture wasstirred for forty-five minutes, and there was added dropwise, at roomtemperature and over a period of one-half hour, a solution of 23.2 g. ofn-octyl isocyanate in 100 ml. of dry acetone. The reaction mixture thusobtained was stirred at room temperature for three hours and then wasevaporated under reduced pressure to reduce its volume by half andpoured into 250 ml. of cold water. (In following this procedure in thepreparation of related species of this invention, it was found in someinstances that instead of pouring the reaction product into water it wasdesirable and in some cases necessary for ready recovery of the productto evaporate the reaction mixture of dryness and then purify theresulting residue). The mixture was chilled in a refrigerator overnight.The solid precipitate which formed was collected on a filter, washedwith cold water, and dried. The dry solid was dissolved in 250 ml. ofwarm diethyl ether, and the solution was treated with decolorizingcharcoal and filtered. The filtrate was warmed to evaporate off about100 ml. of ether and cold petroleum ether was added gradually until aslight turbidity was produced. The mixture was cooled and the solidwhich precipitated was collected on a filter and dried in a vacuumdesiccator. The solid thus obtained, which weighed 28.5 g., wasrecrystallized from diethyl ether-petroleum ether mixture to yield 24.1g. of 1-amidino-3-n-octylurea, having the structural formula ##STR6## asa white crystalline solid which melted at 102°-106° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. It was solublein 95 percent ethyl alcohol at 25° C. to the extent of 5 percent (w/v);a precipitate formed when the 5 percent alcoholic solution was dilutedwith four volumes of water.

B. When an equivalent amount of n-octyl isothiocyanate is substitutedfor the n-octyl isocyanate in the procedure described in part A above,there is obtained as the product 1-amidino-3-n-octylthiourea, having thestructural formula ##STR7##

C. When an equivalent amount of iso-octyl isocyanate is substituted forthe n-octyl isocyanate in the procedure described in part A above, thereis obtained as the product 1-amidino-3-iso-octylurea, having thestructural formula ##STR8##

D. When an eqivalent amount of tert-octyl isothiocyanate is substitutedfor the n-octyl isocyanate in the procedure described in part A above,there is obtained as the product 1-amidino-3-tert-octylthiourea, havingthe structural formula ##STR9##

E. When an equivalent amount of cyclohexyl isocyanate is substituted forthe n-octyl isocyanate in the procedure described in part A above, thereis obtained as the product 1-amidino-3-cyclohexylurea, having thestructural formula ##STR10##

F. When an equivalent amount of 2-diethylaminoethyl isocyanate issubstituted for the n-octyl isocyanate in the procedure described inpart A above, there is obtained as the product1-amidino-3-(2-diethylaminoethyl)urea, having the structural formula##STR11##

G. When an equivalent amount of 5-morpholinoamyl isocyanate issubstituted for the n-octyl isocyanate in the procedure described inpart A above, there is obtained as the product1-amidino-3-(5-morpholinoamyl)urea, having the structural formula##STR12##

H. When an equivalent amount of 3-piperidinopropyl isocyanate issubstituted for the n-octyl isocyanate in the procedure described inpart A above, thereis obtained as the product1-amidino-3-(3-piperidinopropyl)urea, having the structural formula##STR13##

EXAMPLE 2

A. Proceeding in a manner similar to that described above in Example 1,and using 3.2 g. of sodium, 14.3 g. of guanidine hydrochloride, and 18.3g. of n-nonyl isocyanate, there was obtained 18.5 g. of1-amidino-3-n-nonylurea, having the structural formula ##STR14## as awhite crystalline solid which melted at 104°-105° C.

The solubility of this base in water at 25° C. was less than 0.25percent. In 95 percent ethyl alcohol at 25° C., it was soluble to theextent of 5 percent (w/v); a precipitate formed when the 5 percentalcoholic solution was diluted with four volumes of water.

B. By treatment of 1-amidino-3-n-nonylurea with hydrobromic acid inisopropyl alcohol there was obtained 1-amidino-3-n-nonylureahydrobromide as a white crystalline solid which melted at 80°-82° C.This salt was soluble in water at 25° C. to the extent of 1 percent. ThepH of the 1 percent solution was 4.7; when the pH was gradually raisedby addition of n/10 sodium hydroxide solution, a precipitate formed atpH 6.5.

C. When an equivalent amount of iso-nonyl isothiocyanate is substitutedfor the n-nonyl isocyanate in the procedure described in part A above,there is obtained as the product 1-amidino-3-iso-nonylthiourea, havingthe structural formula ##STR15##

Example 3

A. Proceeding in a manner similar to that described above in Example 1,and using 3.2 g. of sodium, 14.3 g. of guanidine hydrochloride, and 18.3g. of n-decyl isocyanate, there was obtained 17.5 g. of1-amidino-3-n-decylurea, having the structural formula ##STR16## as awhite crystalline solid which melted at 110°-112° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. In 95 percentethyl alcohol at 25° C., it was soluble to the extent of 5 percent(w/v); a precipitate formed when the 5 percent alcoholic solution wasdiluted with four volumes of water.

B. The hydrobromide of the above base was prepared as follows: 10 g. of1-amidino-3-n-decylurea was dissolved in 80 ml. of warm methyl alcohol.The resulting solution was cooled to room temperature, and a solution ofhydrogen bromide in diethyl ether was added until the pH of the mixturewas approximately 6. The ether was evaporated off under reducedpressure, and to the oily residue was added 200 ml. of anhydrous diethylether. The mixture was filtered to collect the solid which formed. Thesolid thus collected, which weighed 12 g., was dissolved in 30 ml. ofwarm methyl alcohol, 400 ml. of anhydrous diethyl ether was added, andthe mixture was cooled. The solid which precipitated from solution wascollected on a filter, dried overnight in a vacuum oven at 35° C. Therewas thus obtained 9.4 g. of 1-amidino-3-n-decylurea hydrobromide as awhite crystalline solid which melted at 78°-82° C. The solubility ofthis hydrobromide in water at 25° C. was 0.5 percent. The pH of the 0.5percent aqueous solution was 5.0; when N/10 sodium hydroxide solutionwas gradually added to this solution, a precipitate formed at pH 5.5

C. To a solution of 17 g. of 1-amidino-3-n-decylurea in 150 ml. ofmethyl alcohol there was added 5 percent sulfuric acid until the pH ofthe mixture was approximately 3. The mixture was cooled, and the solidwhich precipitated was collected on a filter and recrystallized from 90ml. of methyl alcohol to yield 18 g. of 1-amidino-3-n-decylurea sulfate[(H₂ N--C(=NH)--NH--CO--NH--C₁₀ H₂₁)₂.H₂ SO₄ ] which melted at 131°-132°C. The solubility of this sulfate in water at 25° C. was less than 0.25percent; and its solubility in 95 percent ethyl alcohol at 25° C. wasless than 1 percent (w/v).

EXAMPLE 4

Proceeding in a manner similar to that described above in part A ofExample 1, and using 3.6 g. of sodium, 16.2 g. of guanidinehydrochloride, and 29.8 g. of n-decyl isothiocyanate, there was obtained16.0 g. of 1-amidino-3-n-decylthiourea, having the structural formula##STR17## as a white crystalline solid which melted at 71°-72° C. Thesolubility of this base in water at 25° C. was less than 0.25 percent.In 95 percent ethyl alcohol, at 25° C. it was soluble to the extent of 5percent (w/v); a precipitate formed when the 5 percent alcoholicsolution was diluted with four volumes of water.

EXAMPLE 5

A. Proceeding in a manner similar to that described above in Example 1,and using 4.3 g. of sodium, 19.1 g. of guanidine hydrochloride, and 29.6g. of n-undecyl isocyanate, there was obtained 30 g. of1-amidino-3-n-undecylurea, having the structural formula ##STR18## as awhite crystalline solid which melted at 109°-110° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. In 95 percentethyl alcohol at 25° C., it was soluble to the extent of 5 percent(w/v); a precipitate formed when the 5 percent alcoholic solution wasdiluted with four volumes of water.

B. By adding to a solution of 10 g. of 1-amidino-3-n-undecylurea in 70ml. of methyl alcohol sufficient ethereal solution of hydrogen bromideto give a mixture having pH 5, and isolating and recrystallizing theresultant product from methyl alcohol-diethyl ether mixture, there wasobtained 10.5 g. of 1-amidino-3-n-undecylurea hydrobromide as a whitecrystalline solid which melted at 82°-83° C. The solubility of thishydrobromide in water at 25° C. was less than 0.25 percent. It wassoluble in 95 percent ethyl alcohol at 25° C. to the extent of 5 percent(w/v); a precipitate formed when the 5 percent alcoholic solution wasdiluted with four volumes of water.

EXAMPLE 6

Proceeding in a manner similar to that described above in Example 1, andusing 2.7 g. of sodium 12.4 g. of guanidine hydrochloride, and 21.1 g.of n-dodecyl isocyanate, there was obtained 23.0 g. of1-amidino-3-n-dodecylurea, having the structural formula ##STR19## as awhite crystalline solid which melted at 100°-103° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. Its solubilityin 95 percent ethyl alcohol at 25° C. was less than 1 percent (w/v).

Interaction of this base with hydrogen bromide yielded1-amidino-3-n-dodecylurea hydrobromide as a white crystalline solidwhich melted at 87°-89° C. The solubility of this hydrobromide in waterat 25° C. was less than 0.25 percent. It was soluble in 95 percent ethylalcohol at 25° C. to the extent of 1 percent (w/v); no precipitateformed when the 1 percent alcoholic solution was diluted with fourvolumes of water, the pH of the thus-diluted solution being 4.1.

EXAMPLE 7

Proceeding in a manner similar to that described above in Example 1, andusing 2.7 g. of sodium, 12.4 g. of guanidine hydrochloride, and 22.7 g.of n-dodecyl isothiocyanate, there was obtained 12.8 g. of1-amidino-3-n-dodecylthiourea, having the structural formula ##STR20##as a white crystalline solid which melted at 75°-80° C. The solubilityof this base in water at 25° C. was less than 0.25 percent. In 95percent ethyl alcohol, at 25° C., it was soluble to the extent of 1percent (w/v); a precipitate formed when the 1 percent alcoholicsolution was diluted with four volumes of water.

EXAMPLE 8

A. Proceeding in a manner similar to that described above in Example 1,and using 2.7 g. of sodium, 12.4 g. of guanidine hydrochloride, and 23.9g. of n-tetradecyl isocyanate, there was obtained 20 g. of1-amidino-3-n-tetradecylurea, having the structural formula ##STR21## asa white crystalline solid which melted at 100°-104° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent; and itssolubility in 95 percent ethyl alcohol at 25° C. was less than 1 percent(w/v).

B. Proceeding in a manner similar to that described in Example 1, andusing 2.7 g. of sodium, 12.4 g. of guanidine hydrochloride, and 25.6 g.of n-tetradecyl isothiocyanate, there was obtained 13.7 g. of1-amidino-3-n-tetradecylurea, having the structural formula ##STR22## asa white crystalline solid which melted at 77°-79° C. The solubility ofthis base in water was less than 0.25 percent. In 95 percent ethylalcohol at 25° C., it was soluble to the extent of 5 percent (w/v); aprecipitate formed when the 5 percent alcoholic solution was dilutedwith four volumes of water.

EXAMPLE 9

A. Proceeding in a manner similar to that described above in Example 1,and using 3.4 g. of sodium, 15.3 g. of guanidine hydrochloride, and 30.1g. of n-hexadecyl isocyanate, there was obtained 23.7 g. of1-amidino-3-n-hexadecylurea, have the structural formula ##STR23## as awhite crystalline solid which melted at 107° -109° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. Its solubilityin 95 percent ethyl alcohol at 25° C. was less than 1 percent (w/v).

B. When an equivalent amount of n-hexadecyl isothiocyanate issubstituted for the n-hexadecyl isocyanate in the procedure described inpart A above, there is obtained as the product1-amidino-3-n-hexadecylthiourea, having the structural formula ##STR24##

EXAMPLE 10

A. Proceeding in a manner similar to that described above in Example 1,and using 3.2 g. of sodium, 14.3 of guanidine hydrochloride, and 18.1 g.of 9-decenyl isocyanate, there was obtained 16 g. of1-amidino-3-(9-decenyl)urea, having the structural formula ##STR25## asa white crystalline solid which melted at 94°- 97° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. In 95 percentethyl alcohol at 25° C., it was soluble to the extent of 5 percent(w/v); a precipitate formed when the 5 percent alcoholic solution wasdiluted with four volumes of water.

B. When an equivalent amount of 9-decenyl isothiocyanate is substitutedfor the 9-decenyl isocyanate in the procedure described in part A above,there is obtained as the product 1-amidino-3-(9-decenyl)thiourea, havingthe structural formula ##STR26##

C. When an equivalent amount of 9-octadecenyl isocyanate is substitutedfor the 9-decenyl isocyanate in the procedure described in part A above,there is obtained as the product 1-amidino-3-(9-octadecenyl)urea, havingthe structural formula ##STR27##

D. When an equivalent amount of 9-octadecenyl isothiocyanate issubstituted for the 9-decenyl isocyanate in the procedure described inpart A above, there is obtained as the product1-amidino-3-(9-octadecenyl)thiourea, having the structural formula##STR28##

EXAMPLE 11

A. Proceeding in a manner similar to that described above in Example 1,and using 2.72 g. of sodium, 12.2 g. of guanidine hydrochloride, and18.0 g. of 3-(n-octyloxy)propyl isocyanate, there was obtained 4.0 g. of1-amidino-3-[3-(n-octyloxy)propyl]urea, having the structural formula##STR29## as an off-white powder which melted at 74°-76° C. This basewas soluble in a dilute acidic solution (prepared by mixing 0.36 ml. ofN/2 hydrochloric acid and 0.14 ml. of water) at 25° C. to the extent of10 percent. The pH of a 1 percent solution in the dilute acid was 2.2;no precipitate formed when the pH of this solution was adjusted to 7.0by addition of N/10 sodium hydroxide solution.

B. When an equivalent amount of 3-(n-octyloxy)propyl isothiocyanatesubstituted for the 3-(n-octyloxy)propyl isocyanate in the proceduredescribed in part A above, there is obtained as the product1-amidino-3-[3-(n-octyloxy)propyl]-thiourea, having the structuralformula ##STR30##

C. When an equivalent amount of 6-methoxyhexyl isocyanate is substitutedfor the 3-(n-octyloxy)propyl isocyanate in the procedure described inpart A above, there is obtained as the product1-amidino-3-(6-methoxyhexyl)urea, having the structural formula##STR31##

D. When an equivalent amount of 8-(n-propyloxy)octyl isothiocyanate issubstituted for the 3-(n-octyloxy)propyl isocyanate in the proceduredescribed in part A above, there is obtained as the product1-amidino-3-[8-(n-propyloxy)octyl]-thiourea, having the structuralformula ##STR32##

EXAMPLE 12

A. Proceeding in a manner similar to that described above in Example 1,and using 2.4 g. of sodium, 11.2 g. of guanidine hydrochloride, and 18.0g. of 3-(n-decyloxy)propyl isocyanate, there was obtained 11 g. of1-amidino-3-[3-(n-decyloxy)propyl]urea, having the structural formula##STR33## as a cream colored powder which melted at 78°-82° C. Thesolubility of this base in water at 25° C. was less than 0.25 percent.In 95 percent ethyl alcohol at 25° C., it was soluble to the extent of 5percent (w/v); a precipitate formed when the 5 percent alcoholicsolution was diluted with four volumes of water.

B. When an equivalent amount of 3-(n-decyloxy)propyl isothiocyanate issubstituted for the 3-(n-decyloxy)propyl isocyanate in the proceduredescribed in part A above, there is obtained as the product1-amidino-3[3-(n-decyloxy)propyl]thiourea, having the structural formula##STR34##

C. When an equivalent amount of 7-(n-decyloxy)heptyl isocyanate issubstituted for the 3-(n-decyloxy)propyl isocyanate in the proceduredescribed in part A above, there is obtained as the product1-amidino-3-[7-(n-decyloxy)heptyl]urea, having the structural formula##STR35##

EXAMPLE 13

A. Proceeding in a manner similar to that described above in Example 1,and using 2.5 g. of sodium, 11.1 g. of guanidine hydrochloride, and 20g. of 3-(n-decylthio)propyl isocyanate, there was obtained 18.8 g. of1-amidino-3[3-(n-decylthio)propyl]urea, having the structural formula##STR36## as a white solid which melted at 89°-92° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. In 95 percentethyl alcohol at 25° C., it was soluble to the extent of 5 percent(w/v); a precipitate formed when the 5 percent alcoholic solution wasdiluted with four volumes of water.

B. When an equivalent amount of 3-(n-decylthio)propyl isothiocyanate issubstituted for the 3-(n-decylthio)propyl isocyanate in the proceduredescribed in part A above, there is obtained as the product1-amidino-3-[3-(n-decylthio)propyl]thiourea, having the structuralformula ##STR37##

C. When an equivalent amount of 4-(n-propylthio)butyl isocyanate issubstituted for the 3-(n-decylthio)propyl isocyanate in the proceduredescribed in part A above, there is obtained as the product1-amidino-3-[4-n-propylthio)butyl]urea, having the structural formula##STR38##

EXAMPLE 14

A. A mixture of 22.4 g. of 1-n-decyl-3-cyanoguanidine, 78 ml. ofisopropyl alcohol, and 16 ml. of concentrated hydrochloric acid wasrefluxed for thirty minutes, after which another 6 ml. of concentratedhydrochloric acid was added, and the mixture was refluxed for two hours.The reaction mixture was cooled and was then evaporated under reducedpressure until the mixture began to foam. There was then added 400 ml.of warm water, and the resulting solution was filtered warm throughdiatomaceous earth repeatedly until a clear filtrate was obtained. Thefiltrate, which contained 1-(n-decylamidino)urea hydrochloride dissolvedtherein, was cooled, and the pH was adjusted to approximately 6 byaddition of N sodium hydroxide solution, thereby to neutralize thehydrochloride and generate the free base, 1-(n-decylamidino)urea, havingthe structural formula ##STR39## and then a solution of 20 g. of sodiumnitrate in 40 ml. of water was added with vigorous stirring. The mixturewas chilled for several hours, and the solid which precipitated wascollected on a filter and washed with dilute nitric acid and water. Thesolid was dried under reduced pressure at room temperature (about 25°C.) for four hours and at 30° C. for three hours. This product, whichweighed 36 g., was recrystallized from 400 ml. of acetonitrile and thenfrom 70 ml. of isopropyl alcohol to yield 12.0 g. of1-(n-decylamidino)urea nitrate, as a white crystalline solid whichmelted at 125°-127° C. The solubility of this nitrate in water was lessthan 0.25 percent, and in 95 percent ethyl alcohol its solubility wasless than 1 percent (w/v).

B. When an equivalent amount of 1-n-octyl-3-cyanoguanidine issubstituted for the 1-n-decyl-3-cyanoguanidine in the proceduredescribed in part A above, there are obtained as the products1-(n-octylamidino)urea, having the structural formula ##STR40## and thenitrate salt thereof.

C. When an equivalent amount of 1-(9-decenyl)-3-cyanoguanidine issubstituted for the 1-n-decyl-3-cyanoguanidine in the proceduredescribed in part A above, there are obtained as the products1-(9-decenylamidino)urea, having the structural formula ##STR41## andthe nitrate salt thereof.

D. When an equivalent amount of1-[3-(iso-decyloxy)propyl]-3-cyanoguanidine is substituted for the1-n-decyl-3-cyanoguanidine in the procedure described in part A above,there are obtained as the products1-[3-(iso-decyloxy)propylamidino]urea, having the structural formula##STR42## and the nitrate salt thereof.

E. When an equivalent amount of1-[4-(tert-octylthio)butyl]-3-cyanoguanidine is substituted for the1-n-decyl-3-cyanoguanidine in the procedure described in part A above,there are obtained as the products1-[4-(tert-octylthio)butylamidino]urea, having the structural formula##STR43## and the nitrate salt thereof.

F. When an equivalent amount of 1-cyclooctyl-3-cyanoguanidine issubstituted for the 1-n-decyl-3-cyanoguanidine in the proceduredescribed in part A above, there are obtained as the products1-(cyclooctylamidino)urea, having the structural formula ##STR44## andthe nitrate salt thereof.

G. When an equivalent amount of 1-(2-morpholinoethyl)3-cyanoguanidine issubstituted for the 1-n-decyl-3-cyanoguanidine in the proceduredescribed in part A above, there are obtained as the products1-[(2-morpholinoethyl)amidino]urea, having the structural formula##STR45## and the nitrate salt thereof.

H. When an equivalent amount of 1-(6-piperidinohexyl)3-cyanoguanidine issubstituted for the 1-n-decyl-3-cyanoguanidine in the proceduredescribed in part A above, there are obtained as the products1-[(6-piperidinohexyl)amidino]urea, having the structural formula##STR46## and the nitrate salt thereof.

EXAMPLE 15

Proceeding in a manner similar to that described above in Example 14,and using 25.2 g. of 1-n-dodecyl-3-cyanoguanidine, 68 ml. of isopropylalcohol, and 16 ml. of concentrated hydrochloric acid, there wereobtained 1-(n-dodecylamidino)urea hydrochloride, the free base1-(n-dodecylamidino)urea having the structural formula ##STR47## and1-(n-dodecylamidino)urea nitrate. The nitrate was a white crystallinesolid which melted at 109°-110° C. The solubility of the nitrate inwater at 25° C. was less than 0.25 percent, and in 95 percent ethylalcohol its solubility was less than 1 percent.

EXAMPLE 16

Proceeding in a manner similar to that described above in Example 14,and using 20 g. of 1-n-tetradecyl-3-cyanoguanidine, 70 ml. of isopropylalcohol, and 9 ml. of hydrochloric acid, there was obtained1-(n-tetradecylamidino)urea hydrochloride, the free base1-(n-tetradecylamidino)urea having the structural formula ##STR48## and1-(n-tetradecylamidino)urea nitrate. The nitrate (11 g. yield) wasdissolved in methyl alcohol and sodium hydroxide solution was added toregenerate the free base, 1-n-tetradecyl-3-cyanoguanidine, which wasdissolved in methyl alcohol and treated with ethereal hydrogen bromidesolution to yield 5.2 g. of 1-n-tetradecyl-3-cyanoguanidine hydrobromideas a white crystalline solid which melted at 116°-118° C. The solubilityof the hydrobromide in water at 25° C. was less than 0.25 percent. In 95percent ethyl alcohol at 25° C., the hydrobromide was soluble to theextent of 5 percent (w/v); a precipitate formed slowly when the 5percent alcoholic solution was diluted with four volumes of water.

EXAMPLE 17

A. A mixture of 70 g. of 1-n-octyl-3-cyanoguanidine and 800 ml. of asaturated (at 0° C.) solution of hydrogen sulfide in methyl alcohol isheated at 70°-80° C. in a closed vessel for forty-eight hours. Thereaction mixture thus obtained is evaporated to dryness under reducedpressure leaving a residue consisting of crude1-(n-octylamidino)thiourea, having the structural formula ##STR49##Recrystallization of this product yields the pure base.

B. When an equivalent amount of 1-n-heptadecyl-3-cyanoguanidine issubstituted for the 1-n-octyl-3-cyanoguanidine in the proceduredescribed in part A above, there is obtained as the product1-(n-heptadecylamidino)thiourea having the structural formula ##STR50##

C. When an equivalent amount of 1-[6-(n-hexyloxy)hexyl]-3-cyanoguanidineis substituted for the 1-n-octyl-3-cyanoguanidine in the proceduredescribed in part A above, there is obtained as the product1-[6-(n-hexyloxy)hexylamidino]thiourea, having the structural formula##STR51##

D. When an equivalent amount of 1-[6-(n-nonylthio)hexyl]3-cyanoguanidineis substituted for the 1-n-octyl-3-cyanoguanidine in the proceduredescribed in part A above, there is obtained as the product1-[6-n-nonylthio)hexylamidino]thiourea, having the structural formula##STR52##

E. When an equivalent amount of 1-(7-tetradecenyl)-3-cyanoguanidine issubstituted for the 1-n-octyl-3-cyanoguanidine in the proceduredescribed in part A above, there is obtained as the product1-(7-tetradecenyl)amidinothiourea, having the structural formula##STR53##

EXAMPLE 18

A. To a solution obtained by dissolving 4.6 g. of sodium in 300 ml. ofdry acetone there was added 32.8 g. of n-butylguanidine sulfate and theresulting mixture was stirred for one hour at room temperature. Therewas then added dropwise, over a period of one hour, a solution of 19.8g. of n-butyl isocyanate in 200 ml. of dry acetone, and the mixture thusobtained was stirred overnight at room temperature. (In some instancesit was found preferable to use an equivalent amount of tert-butylalcohol instead of acetone both in the reaction with sodium and as thereaction solvent.) The reaction mixture was evaporated under reducedpressure to reduce its volume by half, after which it was poured into250 ml. of cold water. (In the preparation of related species of thisinvention by this procedure, it was found in some instances that insteadof pouring the reaction product into water it was desirable and in somecases necessary for ready recovery of the product to evaporate thereaction mixture to dryness and then purify the resulting residue). Thered oil which separated from solution was washed twice with water andwas then dissolved in diethyl ether. The ethereal solution was driedover anhydrous calcium sulfate, and the ether was then evaporated fromthe solution to yield 1-n-butylamidino-3-n-butylurea, having thestructural formula ##STR54## as an oil. This base was dissolved inanhydrous diethyl ether and was converted to its sulfate by addition ofa 5 percent ethereal sulfuric acid solution. The resulting solution wasevaporated under reduced pressure, and the pasty residue thus obtainedwas dissolved in 200 ml. of methyl alcohol. The methanolic solution wastreated with decolorizing charcoal and after removal of the charcoal thesolution was evaporated under reduced pressure. The residue wasdissolved in 200 ml. of iospropyl alcohol and the solution wasevaporated under reduced pressure. The sticky residue was dissolved in200 ml. of methyl alcohol and the methanolic solution was saturated withgaseous ammonia. The mixture was filtered to remove ammonium sulfate andthe filtrate was evaporated under reduced pressure to yield a red oil.This oil was dissolved in 100 ml. of anhydrous diethyl ether, 75 ml. ofpetroleum ether was added, and the resulting solid precipitate wascollected on a filter and dried under reduced pressure for four hours at40° C. This product, which weighed 21.7 g., was recrystallized frombenzene (100 ml.)-petroleum ether (80 ml.) and then from 700 ml. ofanhydrous diethyl ether. There was thus obtained 10.3 g. of1-n-butylamidino-3-n-butylurea as a white crystalline solid which meltedat 82°-94° C. From the ethereal mother liquor there was recovered 3.1 g.of the same product. The solubility of this base in water was less than0.5 percent. It was soluble in 95 percent ethyl alcohol to the extent of5 percent (w/v); on addition of four volumes of water to the 5 percentalcoholic solution, the diluted solution, which had a pH of 8.9,remained clear.

B. When an equivalent amount of n-butyl isothiocyanate is used in placeof the n-butyl isocyanate in the procedure described in part A above,the product obtained is 1-n-butylamidino-3-n-butylthiourea, having thestructural formula ##STR55##

C. When an equivalent amount of 9-decenyl isocyanate is used in place ofthe n-butyl isocyanate in the procedure described in part A above, theproduct obtained is 1-n-butylamidino-3-(9-decenyl)urea, having thestructural formula ##STR56##

D. Using the procedure described above in part A, when an equivalentamount of 4-morpholinobutylguanidine sulfate is substituted for then-butylguanidine and an equivalent amount of cyclohexyl isocyanate issubstituted for the n-butyl isocyanate, the product obtained is1-(4-morpholinobutylamidino)-3-cyclohexylurea, having the structuralformula ##STR57##

E. Using the procedure described in part A, when an equivalent amount of12-ethoxydodecylguanidine sulfate is substituted for then-butylguanidine and an equivalent amount of 4-(n-octylthio)butylisocyanate is substituted for the n-butyl isocyanate, the productobtained is 1-(12 -ethoxydodecylamidino)-3-[4-(n-octylthio)butyl]urea,having the structural formula ##STR58##

EXAMPLE 19

Proceeding in a manner similar to that described above in part A ofExample 18, and using 4.5 g. of sodium, 35.6 g. of n-amylguanidinesulfate, and 22.6 g. of n-amyl isocyanate, there was obtained 14.2 g. of1-n-amylamidino-3-n-amylurea having the structural formula ##STR59## asa white crystalline solid which melted at 89°-91° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. In 95 percentethyl alcohol at 25° C. it was soluble to the extent of 5 percent (w/v);a precipitate formed when the 5 percent alcoholic solution was dilutedwith four volumes of water.

EXAMPLE 20

Proceeding in a manner similar to that described above in part A ofExample 18, and using 4.5 g. of sodium, 38.4 g. of n-hexylguanidinesulfate, and 19.8 g. of n-butyl isocyanate, there was obtained 21 g. of1-n-hexylamidino-3-n-butylurea having the structural formula ##STR60##as an off-white crystalline powder which melted at 96°-99° C. Thesolubility of this base in water at 25° C. was less than 0.25 percent.In 95 percent ethyl alcohol at 25° C. it was soluble to the extent of 5percent (w/v); a precipitate formed when the 5 percent alcoholicsolution was diluted with four volumes of water.

EXAMPLE 21

Proceeding in a manner similar to that described above in part A ofExample 18, and using 3.44 g. of sodium, 28.8 g. of n-hexylguanidinesulfate, and 17.0 g. of n-amyl isocyanate, there was obtained 20.0 g. of1-n-hexylamidino-3-n-amylurea having the structural formula ##STR61## asa white crystalline solid which melted at 74°-75° C. The solubility ofthis base in water at 25° C. was less than 0.25 percent. In 95 percentethyl alcohol at 25° C. it was soluble to the extent of 5 percent (w/v);a precipitate formed when the 5 percent alcoholic solution was dilutedwith four volumes of water.

EXAMPLE 22

A. Proceeding in a manner similar to that described above in part A ofExample 18, and using 4.5 g. of sodium, 38.4 g. of n-hexylguanidinesulfate, and 25.4 g. of n-hexyl isocyanate, there was obtained 11.1 g.of 1-n-hexylamidino-3-n-hexylurea having the structural formula##STR62## as a white crystalline solid which melted at 75°-78° C. Thesolubility of this base in water at 25° C. was less than 0.25 percent.In 95 percent ethyl alcohol at 25° C. it was soluble to the extent of 5percent (w/v); a precipitate formed when the 5 percent alcoholicsolution was diluted with four volumes of water.

B. By treatment of 6 g. of 1-n-hexylamidino-3-n-hexylurea with hydrogenchloride in methanolic solution there was obtained 6.3 g. of1-n-hexylamidino-3-n-hexylurea hydrochloride as a white crystallinesolid which melted at 60°-62° C. The solubility of this hydrochloride inwater at 25° C. was less than 0.25 percent. It was soluble in 95 percentethyl alcohol at 25° C. to the extent of 5 percent (w/v); a precipitateformed slowly when the 5 percent alcoholic solution was diluted withfour volumes of water, the pH of the thus-diluted solution being 4.4.

C. By treatment of 6 g. of 1-n-hexylamidino-3-n-hexylurea in methanolicsolution with an ethereal solution of hydrogen bromide there wasobtained 6.5 g. of 1-n-hexylamidino-3-n-hexylurea hydrobromide as awhite crystalline solid which melted at 56°-60° C. The solubility ofthis hydrobromide in water at 25° C. was less than 0.25 percent. It wassoluble in 95 percent ethyl alcohol at 25° C. to the extent of 5 percent(w/v); a precipitate formed slowly when the 5 percent alcoholic solutionwas diluted with four volumes of water, the pH of the thus-dilutedsolution being 4.3.

D. By treatment of 6 g. of 1-n-hexylamidino-3-n-hexylurea with 85percent phosphoric acid in methanolic solution there was obtained 6.2 g.of 1-n-hexylamidino-3-n-hexylurea phosphate as a white crystalline solidwhich melted at 106°-109° C. The solubility of this phosphate in waterat 25° C. was less than 0.25 percent. It was soluble in 95 percent ethylalcohol at 25° C. to the extent of 5 percent (w/v); a precipitate formedwhen the 5 percent alcoholic solution was diluted with four volumes ofwater.

E. By treatment of 6 g. of 1-n-hexylamidino-3-hexylurea with 70 percentglycolic acid in methanolic solution there was obtained 5.5 g. of1-n-hexylamidino-3-n-hexylurea glycolate as a white crystalline solidwhich melted at 94°-98° C. The solubility of this glycolate in water at25° C. was less than 0.25 percent. It was soluble in 95 percent ethylalcohol at 25° C. to the extent of 5 percent (w/v); a precipitate formedwhen the 5 percent alcoholic solution was diluted with four volumes ofwater.

F. By treatment of 6 g. of 1-n-hexylamidino-3-n-hexylurea with 85percent lactic acid in methanolic solution there was obtained 5 g. of1-n-hexylamidino-3-n-hexylurea lactate as a white crystalline solidwhich melted at 65°-69° C. The solubility of this lactate in a diluteacidic solution (prepared by mixing 0.28 ml. of N/2 hydrochloric acidsolution with 19.72 ml. of water) at 25°C. was less than 0.25 percent.It was soluble in 95 percent ethyl alcohol at 25° C. to the extent of 5percent (w/v); a precipitate formed when the 5 percent alcoholicsolution was diluted with four volumes of water.

EXAMPLE 23

Proceeding in a manner similar to that described above in part A ofExample 18, and using 3.44 g. of sodium, 30.9 g. of n-heptylguanidinesulfate, and 19.1 g. of n-hexylisocyanate, there was obtained 26.2 g. of1-n-heptylamidino-3-n-hexylurea having the structural formula ##STR63##as a white crystalline solid which melted at 68°-72° C. The solubilityof this base in a dilute acidic solution (prepared by mixing 0.36 ml. ofN/2 hydrochloric acid and 9.64 ml. of water) at 25° C. was less than0.25 percent. In 95 percent ethyl alcohol at 25° C. it was soluble tothe extent of 5 percent (w/v); a precipitate formed when the 5 percentalcoholic solution was diluted with four volumes of water.

EXAMPLE 24

Proceeding in a manner similar to that described above in part A ofExample 18, 2.7 g. of sodium was dissolved in 250 ml. of dry acetone, 25g. of n-heptylguanidine sulfate was added to the solution, the mixturewas stirred for 15 hours at room temperature; and then a solution of16.9 g. of n-heptyl isocyanate in 200 ml. of acetone was added dropwise,and the reaction mixture was stirred for 3 hours at room temperature.The reaction mixture was evaporated to half-volume under reducedpressure and the mixture was stored in a refrigerator for two weeks. Thesolid which had precipitated was collected on a filter, was washed withwater and a few ml. of acetonitrile, and dried overnight in adesiccator. The yellowish product thus obtained, which weighed 32.2 g.,was mixed with 30 ml. of cold acetonitrile, and the solid was collectedon a filter, dried overnight in a desiccator, and then recrystallizedfrom acetonitrile to yield 23 g. of 1-n-heptylamidino-3-n-heptylureahaving the structural formula ##STR64## as a white crystalline solidwhich melted at 56°-59° C. This base in methanolic solution was treatedwith ethereal hydrogen chloride solution to yield 21.3 g. of1-n-heptylamidino-3-n-heptylurea hydrochloride as a white crystallinesolid which melted at 71°-° C. The solubility of this hydrochloride indilute aqueous alkali (prepared by mixing 0.30 ml. of N/2 sodiumhydroxide solution with 19.70 ml. of water) at 25° C. was less than 0.25percent. In 95 percent ethyl alcohol at 25° C. this salt was soluble tothe extent of 5 percent (w/v); a precipitate formed when the 5 percentalcoholic solution was diluted with four volumes of water.

EXAMPLE 25

A. 3.68 g. of sodium and 1050 ml. of dry t-butyl alcohol were heatedtogether under reflux with vigorous stirring for about two hours. Theliquid was cooled to approximately 28° C. and then 25 g. of(3-morpholinopropyl)guanidine sulfate was added in one portion. Afterstirring the mixture for thirty minutes, a solution of 9.85 g. ofn-octyl isocyanate in 100 ml. of t-butyl alcohol was added dropwise overa period of twenty minutes. The resulting reaction mixture was stirredfor two and one-half hours and allowed to stand overnight. The mixturewas concentrated on a water bath at 35°-45° C. The residue was mixedwith 250 ml. of acetonitrile and allowed to stand overnight. The mixturewas filtered to remove 16.2 g. of solid, and the acetonitrile wasdistilled from the filtrate to yield 23 g. of a light-brown syrupconsisting of crude 1-[(3-morpholinopropyl)amidino]-3-n-octylurea,having the structural formula ##STR65## Approximately 18 g. of thissyrup was mixed with 500 ml. of anhydrous diethyl ether, the mixture wasfiltered through diatomaceous earth, the filtrate was acidified byaddition of 22 ml. of 4.3N alcoholic hydrogen chloride solution, and themixture was chilled overnight. The solid which had precipitated was thencollected on a filter. This solid, which weighed 17.7 g., wasrecrystallized from isopropyl alcohol, with charcoaling, to yield 12.8g. of solid which was then recrystallized again from isopropyl alcohol.There was thus obtained 9.5 g. of1-[(3-morpholinopropyl)amidino]-3-n-octylurea dihydrochloride as a whitepowder which melted at 141°-143 ° C. (dec.). This salt was soluble inwater at 25° C. to the extent of 20 percent. The pH of the 1 percentaqueous solution was 4.0; when the pH of this solution was graduallyraised by addition of N/10 sodium hydroxide solution, no precipitateformed at pH 7.

B. When an equivalent amount of (2-piperidinoethyl)guanidine sulfate isused instead of (3-morpholinopropyl)guanidine sulfate in the proceduredescribed in part A above, the products obtained are1-[(2-piperidinoethyl)amidino]-3-n-octylurea, having the structuralformula ##STR66## and the dihydrochloride thereof.

C. Following the procedure described in part A above but using anequivalent amount of 4-piperidinobutyl isocyanate in place of n-octylisocyanate, there are obtained as the products1-[(3-morpholinopropyl)amidino]-3-(4-piperidinobutyl)-urea, having thestructural formula ##STR67## and the trihydrochloride thereof.

EXAMPLE 26

Proceeding in a manner similar to that described above in part A ofExample 25, and using 3.68 g. of sodium, 25 g. of(3-morpholinopropyl)guanidine sulfate, and 11.6 g. of n-decylisocyanate, there were obtained1-[(3-morpholinopropyl)amidino]-3-n-decylurea having the structuralformula ##STR68## and the dihydrochloride thereof. The dihydrochloridewas obtained as a white powder which weighed 15.2 g. and which melted at134°-135° C. This salt was soluble in water at 25° C. to the extent of20 percent; the pH of the 1 percent aqueous solution was 4.6, and whenthe pH was gradually raised by addition of N/10 sodium hydroxidesolution no precipitate formed at pH 7.

EXAMPLE 27

Proceeding in a manner similar to that described above in Example 18A,and using 2.3 g. of sodium, 22 g. of n-octylguanidine sulfate, and 15.5g. of n-octyl isocyanate, there was obtained 26 g. of1-n-octylamidino-3-n-octylurea having the structural formula ##STR69##as a white crystalline solid which melted at 60°-62° C. The solubilityof this base in water at 25° C. was less than 0.25 percent. In 95percent ethyl alcohol it was soluble to the extent of 5 percent; aprecipitate formed when the 5 percent ethanolic solution was dilutedwith four volumes of water.

EXAMPLE 28

A. Proceeding in a manner similar to that described above in Example 1,and using 3.4 g. of sodium, 14.3 of guanidine hydrochloride, and 27.7 g.of n-nonyl isothiocyanate, there was obtained 1-amidino-3-n-nonylthiourea, having the structural formula ##STR70## as ared oil.

B. By treatment of 1-amidino-3-n-nonylthiourea with ethereal hydrogenchloride there was obtained 1-amidino-3-n-nonylthiourea hydrochloride asa white crystalline solid which melted at 79°-81° C. The solubility ofthis salt in water at 25° C. was less than 0.25 percent; and itssolubility in 95 percent ethyl alcohol at 25° C. was less than 1 percent(w/v).

EXAMPLE 29

Proceeding in a manner similar to that described above in Example 1, andusing 2.5 g. of sodium, 10.4 of guanidine hydrochloride, and 24.5 g. ofn-undecyl isothiocyanate, there was obtained 15.9 g. of1-amidino-3-n-undecylthiourea, having the structural formula ##STR71##as a white crystalline solid which melted at 71°-72° C. The solubilityof this base in a dilute acidic solution (0.40 ml. of N/2hydrochloricacid plus 19.60 ml. of water) was less than 0.25 percent. In 95 percentethyl alcohol at 25° C., it was soluble to the extent of less than 1percent (w/v).

EXAMPLE 30

Proceeding in a manner similar to that described above in Example 1, andusing 2.9 g. of sodium, 12.9 g. of guanidine hydrochloride, and 17.9 g.of 3-(n-heptyloxy)propyl isocyanate, there was obtained1-amidino-3-[3-(n-heptyloxy)propyl]urea, having the structural formula##STR72## as a white powder which melted at 72°-74° C. This base wassoluble in a dilute acidic solution (0.39 ml. of N/2 hydrochloric acidplus 0.61 ml. of water) at 25° C. to the extent of 5 percent. In 95percent ethyl alcohol at 25° C., it was soluble to the extent of 5percent (w/v); a precipitate formed when the 5 percent alcoholicsolution was diluted with four volumes of water.

EXAMPLE 31

Proceeding in a manner similar to that described above in Example 1, andusing 2.6 g. of sodium, 11.2 g. of guanidine hydrochloride, and 18.0 g.of 3-(n-nonyloxy)propyl isocyanate, there was obtained1-amidino-3-[3-(n-nonyloxy)propyl]urea having the structural formula##STR73## as a white crystalline solid which melted at 77°-78° C. Thisbase was soluble in a dilute acidic solution (0.35 ml. of N/2hydrochloric acid plus 19.65 ml. of water) to less than 0.25 percent. In95 percent ethyl alcohol at 25° C, it was soluble to the extent of 5percent (w/v); a precipitate formed when the 5 percent alcoholicsolution was diluted with four volumes of water.

EXAMPLE 32

A. Proceeding in a manner similar to that described above in Example 1,and using 2.8 g. of sodium, 12.0 g. of guanidine hydrochloride, and 32.0g. of 3-(n-undecyloxy)-propyl isocyanate, there was obtained 15.7 g. of1-amidino-3-[3-(n-undecyloxy)propyl]urea, having the structural formula##STR74## as a white powder which melted at 72°-78° C.

B. Interaction of this base with hydrogen chloride yielded1-amidino-3-[3-(n-undecyloxy)propyl]urea hydrochloride as a white powderwhich melted at 66°-69° C. This hydrochloride was soluble in water at25° C. to the extent of 20 percent. The pH of a 1 percent aqueoussolution was 3.7; when N/10 sodium hydroxide solution was graduallyadded to this solution, a precipitate formed at pH 5.5.

EXAMPLE 33

A. Proceeding in a manner similar to that described above in Example 1,and using 3.0 g. of sodium, 13.0 g. of guanidine hydrochloride, and 36.6g. of 3-(n-dodecyloxy)propyl isocyanate, there was obtained1-amidino-3-[3-(n-dodecyloxy)propyl]urea, having the structural formula##STR75## as a white powder which melted at 76°-80° C.

B. By treatment of 6.5 g. of 1-amidino-3-[3-(n-dodecyloxy)propyl]urea inethyl alcohol solution of hydrogen chloride, there was obtained 5.0 g.of 1-amidino-3-[3-(n-dodecyloxy)propyl]urea hydrochloride as a whitepowder which melted at 59°-61° C. This hydrochloride was soluble inwater at 25° C. to the extent of 20 percent. The pH of a 1 percentaqueous solution was 3.9; when N/10 sodium hydroxide solution wasgradually added to this solution, a precipitate formed at pH 4.8.

EXAMPLE 34

Proceeding in a manner similar to that described above in Example 1, andusing 2.3 g. of sodium, 9.5 g. of guanidine hydrochloride, and 20.0 g.of 3-(n-hexylthio)propyl isocyanate, there was obtained1-amidino-3-[3-(n-hexylthio)-propyl]urea, having the structural formula##STR76## as a white crystalline solid which melted at 71°-73° C. Thesolubility of this base in a dilute acidic solution (0.78 ml. of N/2hydrochloric acid plus 19.72 ml. of water) at 25° C. was less than 0.25percent. In 95 percent ethyl alcohol at 25° C., it was soluble to theextent of 5 percent (w/v); a precipitate formed when the 5 percentalcoholic solution was diluted with four volumes of water.

EXAMPLE 35

Proceeding in a manner similar to that described above in Example 1, andusing 1.06 g. of sodium, 4.45 g. of guanidine hydrochloride, and 10.0 g.of 3-(n-heptylthio)propyl isocyanate, there was obtained 1-amidino-3-[3-(n-heptylthio)propyl]urea having the structural formula ##STR77## asa white crystalline solid which melted at 79°-82° C. The solubility ofthis base in a dilute acidic solution (0.40 ml. of N/2 hydrochloric acidplus 19.60 ml. of water) at 25° C. was less than 0.25 percent. In 95percent ethyl alcohol at 25° C., it was soluble to the extent of 5percent (w/v); a precipitate formed when the 5 percent alcoholicsolution was diluted with four volumes of water.

EXAMPLE 36

Proceeding in a manner similar to that described above in Example 1, andusing 3.4 g. of sodium, 14.3 g. of guanidine hydrochloride, and 34.3 g.of 3-(n-octylthio)propyl isocyanate, there was obtained 22.0 g. of1-amidino-3-[3-(n-octylthio)propyl]urea having the structural formula##STR78## as a white crystalline solid which melted at 84°-85° C. Thesolubility of this base in a dilute acidic solution (0.35 ml. of N/2hydrochloric acid plus 19.65 ml. of water) at 25° C. was less than 0.25percent. In 95 percent ethyl alcohol at 25° C., it was soluble to theextent of 5 percent (w/v); a precipitate formed when the 5 percentalcoholic solution was diluted with four volumes of water.

EXAMPLE 37

Proceeding in a manner similar to that described in Example 1, and using2.3 g. of sodium, 9.5 g. of guanidine hydrochloride, and 22.9 g. of3-(n-nonylthio)propyl isocyanate, there was obtained 19.7 g. of1-amidino-3-[3-(n-nonylthio)propyl]urea, having the structural formula##STR79## as a white crystalline solid which melted at 86°-88° C. Thesolubility of this base in a dilute acidic solution (0.34 ml. of N/2hydrochloric acid plus 19.66 ml. of water) at 25° C. was less than 0.25percent. In 95 percent ethyl alcohol at 25° C., it was soluble to theextent of 5 percent (w/v); a precipitate formed when the 5 percentalcoholic solution was diluted with four volumes of water.

EXAMPLE 38

Proceeding in a manner similar to that described above in Example 1, andusing 2.3 g. of sodium, 9.5 g. of guanidine hydrochloride, and 27.1 g.of 3-(n-undecylthio)propyl isocyanate, there was obtained 16.6 g. of 1-amidino-3-[3-(n-undecylthio)propyl]urea, having the structural formula##STR80## as a white crystalline solid which melted at 91°-93° C. Thesolubility of this base in a dilute acidic solution (0.30 ml. of N/2hydrochloric acid plus 19.70 ml. of water) at 25° C. was less than 0.25percent. In 95 percent ethyl alcohol at 25° C., it was soluble to theextent of 5 percent (w/v); a precipitate formed when the 5 percentalcoholic solution ws diluted in four volumes of water.

EXAMPLE 39

Proceeding in a manner similar to that described above in Example 1, andusing 2.3 g. of sodium, 9.5 g. of guanidine hydrochloride, and 28.5 g.of 3-(n-dodecylthio)propyl isocyanate, there was obtained 28.5 g. of1-amidino-3-[3-(n-dodecylthio)propyl]urea, having the structural formula##STR81## as a white crystalline solid which melted at 91°-92° C. Thesolubility of this base in a dilute acidic solution (0.30 ml. of N/2hydrochloric acid plus 19.70 ml. of water) at 25° C. was less than 0.25percent. In 95 percent ethyl alcohol at 25° C., it was soluble to theextent of 5 percent (w/v); a precipitate formed when the 5 percentalcoholic solution was diluted with four volumes of water.

EXAMPLE 40

Proceeding in a manner similar to that described above in part A ofExample 25, and using 1.96 g. of sodium,, 12.5 g. of(3-morpholinopropyl)guanidine sulfate, and 7.2 g. of n-nonyl isocyanate,there was obtained 1-[(3-morpholinopropyl)amidino]-3-n-nonylurea havingthe structural formula ##STR82## and the dihydrochloride thereof. Thedihydrochloride was obtained as a white powder which melted at 139°-141°C. This salt was soluble in water at 25° C. to the extent of 20 percent;the pH of the 1 percent aqueous solution was 3.5, and when the pH wasgradually raised by addition of N/10 sodium hydroxide solution, noprecipitate formed at pH 7.

EXAMPLE 41

Proceeding in a manner similar to that described above in part A ofExample 25, and using 1.96 g. of sodium, 12.5 g. of(3-morpholinopropyl)guanidine sulfate, and 8.4 g. n-undecylisocyanate,there was obtained 1-[(3-morpholinopropyl)amidino]-3-n-undecylureahaving the structural formula ##STR83## and the dihydrochloride thereof.The dihydrochloride was obtained as a white powder which weighed 9.7 g.and which melted at 143°-145° C. The salt was soluble in water at 25° C.to the extent of 20 percent; the pH of the 1 percent aqueous solutionwas 3.8, and when the pH was gradually raised by addition of N/10 sodiumhydroxide solution, no precipitate formed at pH 6.3.

EXAMPLE 42

Proceeding in a manner similar to that described above in part A ofExample 25, and using 1.96 g. of sodium, 12.5 g. of(3-morpholinopropyl)guanidine sulfate, and 8.95 g. ofn-dodecylisocyanate, there was obtained1-[(3-morpholinopropyl)amidino]-3-n-dodecylurea having the structuralformula ##STR84## and the dihydrochloride thereof. The dihydrochloridewas obtained as a white powder which weighed 5.9 g. and which melted at132°-135° C. This salt was soluble in water at 25° C. to the extent of20 percent; the pH of the 1 percent aqueous solution was 3.8, and whenthe pH was gradually raised by addition of N/10 sodium hydroxidesolution, no precipitate formed at pH 7.6.

Proceeding in accordance with the procedures described hereinabove andusing the appropriate reactants, there are obtained the followingfurther illustrative species of the compounds of Formulas I, II and IIIof the instant invention:

(1) 1-n-hexylamidino-3-(3,3-dimethylallyl)urea

(2) 1-(4-dimethylaminobutylamidino)-3-cyclopropylurea

(3) 1-(9-decenylamidino)-3-(9-decenyl)urea

(4) 1-cyclohexylamidino-3-cyclopentylurea

(5) 1-cycloheptylamidino-3-[4-(n-amyloxy)butyl]urea

(6) 1-(3-morpholinopropylamidino)-3-(3-octenyl)thiourea

(7) 1-(3-piperidinopropylamidino)-3-(3-piperidinopropyl)thiourea

(8) 1-n-hexylamidino-3-n-hexylthiourea

(9) 1-n-heptylamidino-3-n-heptylthiourea

(10) 1-tert-octylamidino-3-(3-morpholinopropyl)urea

(11) 1-[3-(n-octyloxy)propylamidino]-3-(3-morpholinopropyl)urea

(12) 1-(cyclobutylamidino)-3-[3-(n-decyloxy)propyl]thiourea

(13) 1-(8-dimethylaminooctylamidino)-3-[3-(n-decylthio)propyl]thiourea

(14) 1-n-octylamidino-3-(3-propoxypropyl)urea

(15) 1-iso-heptylamidino-3-[4-(propylthio)butyl]urea

(16) 1-n-heptylamidino-3-(2-diisopropylaminoethyl)thiourea

(17) 1-cyclopentylamidino-3-n-undecylurea

(18) 1-cyclopropylamidino-3-(3-piperidinobutyl)urea

(19) 1-(3-morpholinopropylamidino)-3-(4-morpholinobutyl)urea

(20) 1-(2-diethylaminoethylamidino)-3-(2-diethylaminoethyl)thiourea

(21) 1-(2-dimethylaminopropylamidino)-3-(3-morpholinopropyl)thiourea

(22) 1-[3-(n-decylthio)propylamidino]-3-[3-(n-decylthio)propyl]urea

(23) 1-[3-(n-decylthio)propylamidino]-3-cyclohexylurea

(24) 1-[4-n-nonylthio)butylamidino]-3-(5-morpholinoamyl)urea

(25) 1-[3-(n-octyloxy)propylamidino]-3-[3-(n-octyloxy)propyl]urea

(26) 1-[3-(n-heptyloxy)propylamidino]-3-(10-undecenyl)urea

(27) 1-cyclopentylamidino-3-(3,3-dimethylallyl)urea

(28) 1-[(3-hexenyl)amidino]-3-[3-(n-dodecylthio)propyl]urea

(29) 1-(3-di-n-butylaminopropylamidino)-3-(4-octenyl)urea

(30) 1-methallylamidino-3-(3-piperidinopropyl)urea

(31) 1-(2-piperidinoethylamidino)-3-(3-diethylaminopropyl)thiourea

(32) 1-(3-piperidinopropylamidino)-3-[4-(n-propyloxy)butyl]urea

(33) 1-methylamidino-3-(2-ethylhexyl)urea

(34) 1-ethylamidino-3-isohexylthiourea

(35) 1-n-heptylamidino-3-methylurea

(36) 1-(n-tetracosanylamidino)urea

(37) 1-amidino-3-n-tetracosanylurea

(38) 1-n-docosanylamidino-3-methylthiourea

(39) 1-[(2-ethylhexyl)amidino]urea

(40) 1-amidino-2-(2-ethylhexyl)urea

Following are representative results obtained when the compoundsprepared in accordance with the instant invention were tested in vitroby standard serial dilution procedures for bacteriostatic (Bs),bactericidal (Bc), fungistatic (Fs), and fungicidal (Fc) properties;these results are expressed as minimum concentration of the testcompound, in parts per million, required for no growth of the testorganism. For example, in antibacterial tests, using Staphylococcusaureus 209, Salmonella typhosa Hopkins, Clostridium welchii M, andPseudomonas aeruginosa 211, the results obtained were as follows:

    __________________________________________________________________________    Compound of                                                                           Staph. aureus                                                                          Sal. typosa                                                                             Cl. welchii                                                                            Ps. aerug.                                Example No.                                                                           Bs  Bc   Bs   Bc   Bs   Bc  Bs  Bc                                    __________________________________________________________________________    1A      25  25   10   25   10   25  25  25                                    2A      5   7.5  5    5    7.5  7.5 7.5 7.5                                   3A      2.5 10   2.5  10   2.5  2.5 5   10                                    4       5   10   25   25   2.5  2.5 75  >100                                  5A      2.5 2.5  5    5    2.5  2.5 250 1000                                  6A      2.5 75   5    75   50   50  100 >100                                  7       25  25   25   75   2.5  2.5 250 250                                   8A      5   100  50   >100 7.5  7.5 750 >1000                                 8B      10  50   750  >1000                                                                              5    5   500 >1000                                 9A      500 >1000                                                                              1000 >1000                                                                              25   25  1000                                                                              >1000                                 10A     7.5 7.5  7.5  7.5  7.5  7.5 7.5 25                                    11A     50  50   10   25   10   25  50  50                                    12A     5   7.5  5    7.5  5    5   25  25                                    13A     7.5 25   7.5  10   5    5   50  75                                    14A (. HNO.sub. 3)                                                                    10  50   10   25   10   10  50  50                                    15 (. HNO.sub.3)                                                                      7.5 75   7.5  10   5    5   50  75                                    16 (. HBr)                                                                            7.5 25   10   50   5    5   75  100                                   18A     250 250  250  500  25   250 500 500                                   19      25  50   25   50   7.5  25  250 250                                   20      50  50   25   50   5    25  250 250                                   21      25  25   25   25   2.5  2.5 100 >100                                  22A     5   5    7.5  10   2.5  5   50  75                                    22B     10  20   5    7.5  150* 200 100 100                                   22C     10  100  7.5  15   150* 200 100 100                                   22D     15  15   7.5  10   100* 200 100 150                                   22E     10  15   7.5  10   100* 200 100 150                                   22F     10  20   7.5  15   150* 200 100 100                                   23      5   5    5    5    2.5  2.5 50  100                                   24      5   25   5    7.5  2.5  2.5 50  75                                    25 (. 2HCl)                                                                           50  75   50   50   10   10  >100                                                                              --                                    26 (. 2HCl)                                                                           7.5 25   10   25   2.5  2.5 100 100                                   27      7.5 50   7.5  10   5    5   >100                                                                              --                                    28B (. HCl)                                                                           5   --   10** --   50*  --  75  --                                    29      0.75                                                                              --   25** --   75*  --  >100                                                                              --                                    30      25  50   50** 50   75*  >100                                                                              50  100                                   31      5   10   5**  10   100* >100                                                                              25  50                                    32B (. HCl)                                                                           --  --   50** --   >100*                                                                              --  75  --                                    33B (. HCl)                                                                           5   --   25** --   >100*                                                                              --  75  --                                    34      25  --   10   --   75*  --  50  --                                    35      5   25   7.5**                                                                              7.5  50*  75  50  50                                    36      5   7.5  7.5**                                                                              7.5  75*  100 25  50                                    37      5   10   25** 25   100* >100                                                                              25  50                                    38      7.5 50   50** 50   >100*                                                                              --  75  100                                   39      10  75   50** 75   >100*                                                                              --  75  >100                                  40 (. 2HCl)                                                                           12.5                                                                              --   12.5**                                                                             --   >100*                                                                              --  100 --                                    41 (. 2HCl)                                                                           2.5 --   25** --   >100*                                                                              --  >100                                                                              --                                    42 (. 2HCl)                                                                           5   --   2.5**                                                                              --   >100*                                                                              --  >100                                                                              --                                    __________________________________________________________________________     *Proteus vulgaris ATCC 9920 was used instead of Cl. welchii.                  **Escherichia coli was used instead of Sal.typhosa.                      

In antifungal tests, using Trichophyton mentagrophytes, Aspergillusniger, and Monilia albicans, the following results were obtained:

    ______________________________________                                        Compound of                                                                             T. mentag. As. niger   Mon. alb.                                    Example No.                                                                             Fs     Fc      Fs    Fc    Fs    Fc                                 ______________________________________                                        1A        100    100     --    --    --    --                                 3A        10     10      1000  >1000 100   1000                               5A        10     10      1000  1000  100   1000                               7         10     100     100   100   100   100                                8B        100    100     1000  >1000 1000  >1000                              11A       100    100     100   100   100   100                                12A       100    100     100   100   100   100                                13A       100    100     100   100   100   100                                14A (. HNO.sub.3)                                                                       100    100     >100  --    100   >100                               15 (. HNO.sub.3)                                                                        10     10      100   >100  10    100                                16 (. HBr)                                                                              10     100     100   100   10    100                                18A       1000   1000    1000  1000  1000  1000                               21        100    100     100   100   100   100                                22A       100    100     100   >100  100   100                                23        100    100     100   100   100   100                                24        10     10      100   100   10    100                                25        100    100     1000  1000  1000  1000                               26        100    100     100   100   100   100                                27        100    100     100   >100  >100  --                                 28B (. HCl)                                                                             5      --      12.5  --    12.5  --                                 29        5      --      100   --    50    --                                 30        75     --      >100  --    100   --                                 31        25     --      50    --    25    --                                 32B (. HCl)                                                                             75     --      >100  --    100   --                                 33B (. HCl)                                                                             50     --      >100  --    50    --                                 34        50     --      100   --    100   --                                 35        25     25      75    75    50    50                                 40 (. 2HCl)                                                                             50     --      >100  --    >100  --                                 41 (. 2HCl)                                                                             7.5    --      50    --    75    --                                 42 (. 2HCl)                                                                             12.5   --      >100  --    50    --                                 ______________________________________                                    

When an aqueous solution of one pound of 1-amidino-3-n-decylureahydrobromide in 100 gallons of water was sprayed onto the foliage oftomato plants, 68 percent protection was afforded against infection byXanthomonas vesicatoria (bacterial spot). When the same compound atone-quarter pound per 100 gallons of water was similarly applied totomato plants, 99 percent of the plants were protected against infectionby Phytophthora infestans (late blight). And when this same compound atone-quarter pound per 100 gallons of water was similarly applied topinto beans, 86 percent protection was afforded against infection byUromyces phaseoli typica (bean rust).

1-Amidino-3-n-dodecylthiourea was found to afford good protectionagainst bacterial spot in tomato plants.

In commercial paper pulp having a native population of approximately onemillion organisms per gram, all organisms in the pulp were killed withinone hour by 10 parts per million of 1-amidino-3-n-undecylureahydrobromide, thus indicating the usefulness of this compound as a slimecontrol agent in paper making.

We claim:
 1. A compound having the structural formula ##STR85## whereinX is oxygen or sulfur; one of Y" and Y'" is morpholinoalkyl containing6-10 carbon atoms and the other of Y" and Y'" is a member of the groupconsisting of alkyl containing 1-18 carbon atoms, alkenyl containing3-18 carbon atoms, alkoxyalkyl containing 3-17 carbon atoms,alkylthioalkyl containing 3-17 carbon atoms, cycloalkyl containing 3-8carbon atoms, di(lower alkyl)aminoalkyl containing 4-10 carbon atoms andmorpholinoalkyl containing 6-10 carbon atoms; and Y" also is hydrogenwhen Y'" is morpholinoalkyl containing 6-10 carbon atoms.
 2. A compoundaccording to claim 1 wherein X is oxygen, Y" is morpholinoalkylcontaining 6-10 carbon atoms and Y'" is alkyl containing 1-18 carbonatoms.
 3. A compound according to claim 2 wherein Y" is3-morpholinopropyl and Y'" is n-octyl, n-nonyl, n-decyl, n-undecyl orn-dodecyl.